A proposed role for VEGF isoforms in sex-specific vasculature development in the gonad

Abstract

Many scientists have expended efforts to determine what regulates development of an indifferent gonad into either a testis or ovary. Expression of Sry and upregulation of Sox9 are factors that initiate formation of the testis-specific pathway to allow for both sex-specific vasculature and seminiferous cord formation. Migration of mesonephric precursors of peritubular myoid cells and endothelial cells into the differentiating testis is a critical step in formation of both of these structures. Furthermore, these events appear to be initiated downstream from Sry expression. Sertoli cell secretion of growth factors acts to attract these mesonephric cells. One hypothesis is that a growth factor specific for these cell linages act in concert to coordinate migration of both peritubular and endothelial cells. A second hypothesis is that several growth factors stimulate migration and differentiation of mesonephric 'stem-like' cells to result in migration and differentiation into several different cell lineages. While the specific mechanism is unclear, several growth factors have been implicated in the initiation of mesonephric cell migration. This review will focus on the proposed mechanisms of a growth factor, Vascular Endothelial Growth Factor, and how different angiogenic and inhibitory isoforms from this single gene may aid in development of testis-specific vascular development.

Figure 1

Sry-regulated events occurring during sex determination and testis morphogenesis using days postcoitum and tail somites as developmental markers (modified from Cupp and Skinner 2005.)

Figure 2

Genes demonstrated to be involved in sex-specific vascular patterns through development of null mice or treatment of indifferent gonads in organ culture.

Figure 3

Exons in VEGF gene that compose each VEGF isoform.